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Based on the information I've gathered, I'll now review the GO-CAM model gomodel:653b0ce600000382 "TAX1BP1-mediated degradation of MAVS by E3 ligase ITCH (Human)".

Review of GO-CAM Model: TAX1BP1-mediated degradation of MAVS by E3 ligase ITCH (Human)

Model ID: gomodel:653b0ce600000382

Model Summary:

This model represents how TAX1BP1 mediates the degradation of MAVS (Mitochondrial antiviral-signaling protein) by the E3 ubiquitin ligase ITCH in human cells. The model involves four key proteins and their respective activities:

  1. MAVS (UniProtKB:Q7Z434) - signaling adaptor activity
  2. TAX1BP1 (UniProtKB:Q86VP1) - protein-macromolecule adaptor activity
  3. ITCH (UniProtKB:Q96J02) - ubiquitin protein ligase activity
  4. TRAF3IP3 (UniProtKB:Q9Y228) - molecular adaptor activity

Evaluation of Model Accuracy and Completeness:

Biological Content:

The model correctly captures the biological relationship described in the literature where TAX1BP1 acts as an adaptor to facilitate ITCH-mediated ubiquitination and degradation of MAVS. This is supported by the evidence cited in the model, particularly PMID:27736772, which describes TAX1BP1's role in restraining virus-induced apoptosis by facilitating ITCH-mediated degradation of MAVS.

Molecular Functions and Locations:

  • MAVS is correctly annotated with "signaling adaptor activity" (GO:0035591) and located in the mitochondrion (GO:0005739), which aligns with its known function and localization.
  • TAX1BP1 is properly annotated with "protein-macromolecule adaptor activity" (GO:0030674) and also located in the mitochondrion, which is consistent with its role in facilitating ITCH-mediated degradation of MAVS.
  • ITCH is annotated with "ubiquitin protein ligase activity" (GO:0061630) and located in the mitochondrion, which accurately represents its role in ubiquitinating MAVS.
  • TRAF3IP3 is annotated with "molecular adaptor activity" (GO:0060090) and located in the mitochondrion, which is consistent with its role in the model.

Causal Relationships:

The model correctly uses the following causal relations: - TAX1BP1's adaptor activity "provides input for" (RO:0002413) ITCH's ubiquitin ligase activity, which is appropriate for an adaptor that brings together an enzyme and its substrate. - ITCH's ubiquitin ligase activity "directly negatively regulates" (RO:0002630) MAVS's signaling adaptor activity, which correctly represents ITCH-mediated degradation of MAVS. - MAVS's signaling adaptor activity "directly positively regulates" (RO:0002629) TRAF3IP3's molecular adaptor activity, which accurately reflects MAVS's role in activating downstream signaling components.

Process Annotations:

  • MAVS and TRAF3IP3 are both annotated as part of "cytoplasmic pattern recognition receptor signaling pathway" (GO:0002753), which is accurate.
  • TAX1BP1 is annotated as part of "negative regulation of cytoplasmic pattern recognition receptor signaling pathway" (GO:0039532), which correctly represents its role in downregulating MAVS-mediated signaling.
  • ITCH is annotated as part of "protein K48-linked ubiquitination" (GO:0070936), which is the appropriate process for its role in targeting MAVS for degradation.

Adherence to GO-CAM Best Practices:

  1. Molecular Adaptors Annotation: The model correctly follows the guidelines for annotating molecular adaptors. Both TAX1BP1 and TRAF3IP3 are annotated with appropriate adaptor molecular functions, and the "provides input for" relation is correctly used for TAX1BP1's role in facilitating ITCH's activity.

  2. Complex Representation: The model doesn't explicitly represent any protein complexes but correctly represents the individual proteins and their respective activities, which is appropriate given that specific protein-protein interactions rather than stable complexes are being modeled.

  3. Evidence: Each activity and causal relationship is supported by appropriate evidence codes and PMID references, which is in line with GO-CAM best practices.

  4. Biological Pathway Representation: The model represents a cohesive biological pathway with clear directionality from MAVS to TRAF3IP3, with regulatory inputs from TAX1BP1 and ITCH, making it easy to understand the overall process.

Suggestions for Improvement:

  1. Consider Additional Context: The model could be enhanced by including more context about what triggers this pathway, such as viral infection, which could be represented as an upstream cause.

  2. Detailed Process Outcomes: The model currently doesn't explicitly show the outcome of MAVS degradation for cellular processes. Adding downstream effects, such as reduced interferon production or inhibition of apoptosis, would provide a more complete picture.

  3. Consider Adding TRAF3: The model mentions TRAF3IP3 but doesn't include TRAF3 itself, which might be relevant given TRAF3's important role in MAVS signaling as indicated by the UniProt entries.

Conclusion:

This GO-CAM model accurately represents the TAX1BP1-mediated degradation of MAVS by the E3 ligase ITCH in human cells. The model adheres to GO-CAM best practices for representing molecular adaptors and signaling pathways. The causal relationships between the activities are appropriately represented with clear directionality. The model includes appropriate evidence for all assertions and correctly represents the subcellular localizations of the proteins involved. Minor enhancements could be made to provide more context and downstream effects, but overall this is a well-constructed GO-CAM model that effectively captures the biological process it aims to represent.